The role of the renin-angiotensin system in hypertensive disease has not been defined. The factors affecting the generation rate of angiotensin in blood or at the tissue level and plasma proteins which might transport the generated peptides in normotensive and hypertensive subjects are therefore centrally involved in the proposed research. The factors regulating the generation of angiotensin (activators or inhibitors) independent of either renin, renin concentration or substrate level is one of the main emphases of the proposed project. Isolation and purification of human renin and particularly its substrate will allow for kinetic evaluation of the reaction following addition of plasma and plasma fractions from normal and hypertensive subjects to determine the presence of modifiers of the reaction and their mode of action. Identification and characterization of naturally occurring modifiers of the reaction will also be carried out. Because of the difficulty in measuring renin and substrate concentrations in plasma, which can be measured only indirectly through their interaction to produce angiotensin, we also propose to use the purified proteins(renin and substrate) to produce specific antisera for their direct immunologic assay. Following similar separation procedures for proteins, we also propose to identify the angiotensin binding proteins of plasma (transport) and specific target tissue (receptors). The possibility that these proteins may be different in normal and hypertensive subjects will also be investigated.